A5028953672- Barrier Structure and Function Studies
- Wnt/β-catenin signaling in development and cancer
- Axon Guidance and Neuronal Signaling
- Kruppel-like factors research
- Neurological Disease Mechanisms and Treatments
- Angiogenesis and VEGF in Cancer
- Drug Transport and Resistance Mechanisms
- Cancer-related molecular mechanisms research
- Hedgehog Signaling Pathway Studies
- Connexins and lens biology
- Pluripotent Stem Cells Research
- Cancer-related gene regulation
- Caveolin-1 and cellular processes
- Neuroinflammation and Neurodegeneration Mechanisms
- Cell Adhesion Molecules Research
- S100 Proteins and Annexins
- Epigenetics and DNA Methylation
- Eicosanoids and Hypertension Pharmacology
- Congenital heart defects research
- MicroRNA in disease regulation
- Bone and Dental Protein Studies
- Nitric Oxide and Endothelin Effects
- Circular RNAs in diseases
- Acute Ischemic Stroke Management
- RNA Research and Splicing
Goethe University Frankfurt
2015-2024
Cardio-Pulmonary Institute
2023-2024
German Centre for Cardiovascular Research
2017-2024
University Hospital Frankfurt
2006-2023
Cardiovascular Center Frankfurt
2019-2021
Frankfurt Cancer Institute
2017-2019
Deutschen Konsortium für Translationale Krebsforschung
2019
Laboratory for Biomedical Neurosciences
2019
Ospedale regionale di Lugano
2019
University of Kentucky
2019
The blood–brain barrier (BBB) is confined to the endothelium of brain capillaries and indispensable for fluid homeostasis neuronal function. In this study, we show that endothelial Wnt/β-catenin (β-cat) signaling regulates induction maintenance BBB characteristics during embryonic postnatal development. Endothelial specific stabilization β-cat in vivo enhances maturation, whereas inactivation causes significant down-regulation claudin3 (Cldn3), up-regulation plamalemma vesicle-associated...
Several platelet-derived growth factor (PDGF) and vascular endothelial (VEGF) family members display C-terminal protein motifs that confer retention of the secreted factors within pericellular space. To address role PDGF-B in vivo, we deleted motif by gene targeting mice. This resulted defective investment pericytes microvessel wall delayed formation renal glomerulus mesangium. Long-term effects lack included severe retinal deterioration, glomerulosclerosis, proteinuria. We conclude...
During heart development endocardial cells within the atrio-ventricular (AV) region undergo TGFβ-dependent epithelial-mesenchymal transformation (EMT) and invade underlying cardiac jelly. This process gives rise to cushions from which AV valves part of septum originate. In this paper we show that in mouse embryos explants TGFβ induction EMT is strongly inhibited mice deficient for endothelial β-catenin, leading a lack cushion formation. Using Wnt-signaling reporter strain, demonstrated vivo...
The blood-brain barrier (BBB) protects the central nervous system (CNS) from harmful blood-borne factors. Although BBB dysfunction is a hallmark of several neurological disorders, therapies to restore function are lacking. An attractive strategy repurpose developmental regulators, such as Wnt7a, into BBB-protective agents. However, safe therapeutic use Wnt ligands complicated by their pleiotropic Frizzled signaling activities. Taking advantage Wnt7a/b-specific Gpr124/Reck co-receptor...
Using the Cre/loxP system we conditionally inactivated β-catenin in endothelial cells. We found that early phases of vasculogenesis and angiogenesis were not affected mutant embryos; however, vascular patterning head, vitelline, umbilical vessels, placenta was altered. In addition, many regions, lumen irregular with formation lacunae at bifurcations, vessels frequently hemorrhagic, fluid extravasation pericardial cavity observed. Cultured −/− cells showed a different organization...
Endothelial Wnt/β-catenin signaling is necessary for angiogenesis of the central nervous system and blood-brain barrier (BBB) differentiation, but its relevance glioma vascularization unknown. In this study, we show that doxycycline-dependent Wnt1 expression in subcutaneous intracranial mouse models induced endothelial led to diminished tumor growth, reduced vascular density, normalized vessels with increased mural cell attachment. These findings were corroborated GL261 cells intracranially...
Reproducing the characteristics and functional responses of blood–brain barrier (BBB) in vitro represents an important task for research community, would be a critical biotechnological breakthrough. Pharmaceutical biotechnology industries provide strong demand inexpensive easy-to-handle BBB models to screen novel drug candidates. Recently, it was shown that canonical Wnt signaling is responsible induction properties neonatal brain microvasculature vivo. In present study, following on from...
Maintenance of the endothelial blood-brain-barrier (BBB) through Wnt/β-catenin signalling is essential for neuronal function. The cells however, providing Wnt growth factors at adult neurovascular unit (NVU) are poorly explored. Here we show by conditionally knocking out evenness interrupted (Evi) gene in astrocytes (EviΔAC) that astrocytic release crucial BBB and NVU integrity. EviΔAC mice developed brain oedema increased vascular tracer leakage. While vascularization junctions were not...
The outcome of stroke is greatly influenced by the state blood–brain barrier (BBB). BBB endothelium sealed paracellularly tight junction (TJ) proteins, i.e., claudins (Cldns) and redox regulator occludin. Functions Cldn3 occludin at are largely unknown, particularly after stroke. We address effects deficiency stress factors on its TJs. tightened for small molecules ions, limited endothelial endocytosis, strengthened TJ structure controlled Cldn1 expression. After middle cerebral artery...
Blood-brain barrier (BBB) dysfunction, characterized by degradation of BBB junctional proteins and increased permeability, is a crucial pathophysiological feature acute ischemic stroke. Dysregulation multiple neurovascular unit (NVU) cell types involved in breakdown stroke that may be further aggravated reperfusion therapy. Therefore, therapeutic co-targeting dysregulated NVU constitutes promising strategy to preserve function improve clinical outcome. However, methods for simultaneous...